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  • Title: Size effect of rebamipide ophthalmic nanodispersions on its therapeutic efficacy for corneal wound healing.
    Author: Nagai N, Ito Y, Okamoto N, Shimomura Y.
    Journal: Exp Eye Res; 2016 Oct; 151():47-53. PubMed ID: 27423550.
    Abstract:
    In a variety of tissues including gastrointestinal mucosa, rebamipide (REB) provides cytoprotection, prevents inflammation, and promotes wound healing. Clinically, REB ophthalmic dispersions are used to treat diabetic keratopathy. In this study, we investigated the optimal particle size of REB to promote corneal wound healing using a model of diabetic keratopathy, the debrided corneal epithelium from Otsuka Long-Evans Tokushima Fatty (OLETF) rats. First, we prepared three dispersions with different REB particle sizes (REB735, REB150, REB45) by treatment with zirconia beads and Bead Smash 12 (a bead mill). The mean particle sizes of the REB735, REB150, REB45 dispersions were approximately 735 nm, 150 nm and 45 nm, respectively. Next, we measured the amounts of REB in the corneal and conjunctival tissues of rats following the instillation of the REB dispersions. The amounts of REB in the corneal and conjunctival tissues following the instillation of REB dispersions was increased by using the mill method, and the amount of REB in rats instilled with the REB150 dispersion was significantly higher than in rats instilled with the REB45 dispersion. Moreover, the corneal wound healing rate for rats instilled with the REB150 dispersion was significantly higher than for rats instilled with the REB735 or REB45 dispersions. In addition, these REB dispersions enhanced corneal epithelial cell growth, resulting an enhancement of corneal wound healing rate. Thus, we found that the ocular drug accumulation and therapeutic effect on corneal wound healing of REB dispersions is enhanced by preparing particles with a size of ca. 150 nm. These findings provide significant information that can be used to design further studies aimed at developing ophthalmic dispersions.
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